Machine learning-based clinical decision support for infection risk prediction.

Background: Healthcare-associated infection (HAI) remains a significant risk for hospitalized patients and a challenging burden for the healthcare system. This study presents a clinical decision support tool that can be used in clinical workflows to proactively engage secondary assessments of pre-symptomatic and at-risk infection patients, thereby enabling earlier diagnosis and treatment. Methods: This study applies machine learning, specifically ensemble-based boosted decision trees, on large retrospective hospital datasets to develop an infection risk score that predicts infection before obvious symptoms present. We extracted a stratified machine learning dataset of 36,782 healthcare-associated infection patients. The model leveraged vital signs, laboratory measurements and demographics to predict HAI before clinical suspicion, defined as the order of a microbiology test or administration of antibiotics. Results: Our best performing infection risk model achieves a cross-validated AUC of 0.88 at 1 h before clinical suspicion and maintains an AUC >0.85 for 48 h before suspicion by aggregating information across demographics and a set of 163 vital signs and laboratory measurements. A second model trained on a reduced feature space comprising demographics and the 36 most frequently measured vital signs and laboratory measurements can still achieve an AUC of 0.86 at 1 h before clinical suspicion. These results compare favorably against using temperature alone and clinical rules such as the quick sequential organ failure assessment (qSOFA) score. Along with the performance results, we also provide an analysis of model interpretability via feature importance rankings. Conclusion: The predictive model aggregates information from multiple physiological parameters such as vital signs and laboratory measurements to provide a continuous risk score of infection that can be deployed in hospitals to provide advance warning of patient deterioration.

Factor analysis as a tool to explore the heterogeneity of type 2 diabetes: A feasibility study.

AIM: Diabetes is currently classified based on pathogenetic mechanisms and Type 2 diabetes (T2DM) can be considered a residual heterogeneous category. Factor analysis (FA) identifies a limited number of calculated variables related to a larger number of measured parameters, capable of explaining most of their variance. Aim of the present study was to verify the feasibility of the application of FA for the development of pathogenetic models of individual cases of T2DM, using three available databases. METHODS: Firstly, a model of FA was applied to an existing dataset of non-diabetic patients, identifying three factors associated with fasting or post-prandial hyperglycemia. These factors were then calculated in: - patients enrolled in a retrospective observational study, assessing time to failure to diabetes treatment in three cohorts of patients (metformin or sulfonylurea monotherapy, or no pharmacological therapy); - in a retrospective cohort of patients failing to dual oral therapy and initiating treatment with DPP4 inhibitors; - in patients enrolled in a case-control study onincident cancer in T2DM subjects initiating insulin treatment. RESULTS AND CONCLUSIONS: Despite limitations, our results confirm the feasibility of approaching the characterization of T2DM through the identification of dimensional factors, providing additional and complementary information to that obtained with cluster analysis.

Radioecological studies of the main naturally occurring radionuclides in the area of Gela Phosphate Industry (Italy) through radioanalytical separation and measurement techniques.

Radioecological studies have been carried out in area of Gela Phosphate Industry. As a part of the project, some achievements have been described in the paper, including: (1) determination of the activity concentrations of 210Po, 210Pb, uranium, and radium isotopes in phosphogypsum, phosphoric acid, soil, and marine sediment, (2) inventory estimation of the NORM in the residual product and by-product, and (3) the radioecological investigation and evaluation on the NORM contamination in the sea area of Gela. The obtained data showed that the 210Po, 210Pb, uranium, and radium isotope contamination due to discharge of phosphogypsum from 1960s to 1990s is not observable through sediment analyses.

Prolonged non-invasive respiratory supports in a COVID-19 patient with severe acute hypoxemic respiratory failure.

A pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 was declared in 2020. Severe cases were characterized by the development of acute hypoxemic respiratory failure (AHRF) requiring advanced respiratory support. However, intensive care units (ICU) were saturated, and many patients had to be treated out of ICU. This case describes a 75-year-old man affected by AHRF due to Coronavirus Disease 2019 (COVID-19), hospitalized in a high-dependency unit, with PaO2/FiO2 <100 for 28 consecutive days. An experienced team with respiratory physiotherapists was in charge of the noninvasive ventilatory support (NIVS). The patient required permanent NIVS with continuous positive airway pressure, non-invasive ventilation, high flow nasal oxygen and body positioning. He was weaned from NIVS after 37 days and started exercise training afterwards. The patient was discharged at home with low-flow oxygen therapy. This case represents an example of a successful treatment of AHRF with the still controversial noninvasive respiratory support in one patient with COVID-19.

Pulse arrival time, a novel sleep cardiovascular marker: the multi-ethnic study of atherosclerosis.

BACKGROUND: Pulse arrival time (PAT) is commonly used to estimate blood pressure response. We hypothesised that PAT response to obstructive respiratory events would be associated with increased cardiovascular risk in people with obstructive sleep apnoea. METHODS: PAT, defined as the time interval between electrocardiography R wave and pulse arrival by photoplethysmography, was measured in the Multi-Ethnic Study of Atherosclerosis Sleep study participants. The PAT response to apnoeas/hypopnoeas was defined as the area under the PAT waveform following respiratory events. Cardiovascular outcomes included markers of subclinical cardiovascular disease (CVD): left ventricular mass, carotid plaque burden score and coronary artery calcification (CAC) (cross-sectional) and incident composite CVD events (prospective). Multivariable logistic and Cox proportional hazard regressions were performed. RESULTS: A total of 1407 participants (mean age 68.4 years, female 47.5%) were included. Higher PAT response (per 1 SD increase) was associated with higher left ventricular mass (5.7 g/m2 higher in fourth vs first quartile, p<0.007), higher carotid plaque burden score (0.37 higher in fourth vs first quartile, p=0.02) and trended to greater odds of CAC (1.44, 95% CI 0.98 to 2.15, p=0.06). A total of 65 incident CVD events were observed over the mean of 4.1 (2.6) years follow-up period. Higher PAT response was associated with increased future CVD events (HR: 1.20, 95% CI 1.02 to 1.42, p=0.03). CONCLUSION: PAT is independently associated with markers of subclinical CVD and incident CVD events. Respiratory-related PAT response is a novel and promising polysomnography metric with cardiovascular implications.

Sensitive and accurate methods for determination of low activity level of 90Sr and 137Cs in grass/vegetable samples.

Sensitive, precise and accurate methods for determination of low activity level of 90Sr and 137Cs in grass/vegetable samples by a low background ß-counter were developed. The method for 90Sr determination was based on coprecipitation as carbonate, elimination of 210Bi and iron with a Microthene-TOA column, separation of 90Y with a Microthene-HDEHP column, and source preparation as Y2(C2O4)3. The method for 137Cs determination was based on Cs adsorption on ammonium molybdophosphate and precipitation as Cs3Bi2I9 for source preparation. The quality control tests indicated that the methods could provide accurate results. The method application showed that: (1) The mean yields of yttrium and cesium were 79 ± 6% and 84 ± 2%, respectively. (2) The activity concentrations of 90Sr in 9 grass/vegetable samples were in the range of 0.04-1.8 Bq kg-1, while that of 137Cs in the range of 0.022-0.18 Bq kg-1. And (3) the uptake rate of 90Sr from soil to grass/vegetable was much higher than that of 137Cs.

Spectral sleep electroencephalographic correlates of sleep efficiency, and discrepancies between actigraphy and self-reported measures, in older men.

Discrepancies between actigraphic and self-reported sleep measures are common. Studies of people with insomnia, in whom both sleep disturbances and discrepancy are common, suggest disturbances and discrepancy reflect differences in the sleeping brain's activity measurable using spectral electroencephalogram (EEG). Disentangling effects of discrepancy and disturbance on sleep EEG could help target research on the consequences and treatments of different sleep phenotypes. We therefore categorized participants in a cohort study including 2,850 men (average age = 76 years, standard deviation = 5.5) into four groups using median splits on actigraphic and self-reported sleep efficiency (SE). We compared spectral power between these groups in 1-Hz bins up to 24 Hz. Compared with the concordant-high SE group: (a) the group with high actigraphic and low self-reported SE had higher spectral power from 11-15 Hz across the night; (b) both groups with low actigraphic SE had higher power across the 15-24 Hz range, predominantly in early cycles, and greater slow frequency power in later cycles. These findings suggest that perceived wakefulness undetected by actigraphy may result from or drive activity corresponding to spindles. We also found, consistent with hyperarousal models, that low SE detectable via actigraphy was related to higher frequency power in the beta range; actigraph-measured inefficiency was also associated with later slow oscillations, potentially representing attempts to dissipate homeostatic drive elevated from earlier hyperarousal. These distinct spectral EEG markers (of low SE measured with actigraphy vs. low perceived SE that is not captured by actigraphy) may have different causes or consequences.

Macro and micro sleep architecture and cognitive performance in older adults.

We sought to determine which facets of sleep neurophysiology were most strongly linked to cognitive performance in 3,819 older adults from two independent cohorts, using whole-night electroencephalography. From over 150 objective sleep metrics, we identified 23 that predicted cognitive performance, and processing speed in particular, with effects that were broadly independent of gross changes in sleep quality and quantity. These metrics included rapid eye movement duration, features of the electroencephalography power spectra derived from multivariate analysis, and spindle and slow oscillation morphology and coupling. These metrics were further embedded within broader associative networks linking sleep with aging and cardiometabolic disease: individuals who, compared with similarly aged peers, had better cognitive performance tended to have profiles of sleep metrics more often seen in younger, healthier individuals. Taken together, our results point to multiple facets of sleep neurophysiology that track coherently with underlying, age-dependent determinants of cognitive and physical health trajectories in older adults.

Genetic mutations in primary malignant melanoma of the esophagus: case report and literature review.

The most frequent genetic aberrations in mucosal melanoma are activating mutations of c-KIT. Primary malignant melanomas of esophagus (PMME) are uncommon entities, with aggressive biological behavior and poor prognosis. The better definition of their genotype could improve therapeutic options. We report a case of a 66 years old man with a PMME in the lower third of the esophagus. Analysis of c-kit, KRAS, NRAS and BRAF genes resulted negative for mutations. On the basis of a computerized (PuMed/Medline) bibliography search we retrieved a total of other 35 cases of PMME analyzed for genetic alterations in RAS, BRAF, and KIT. When we compared mutations frequency of PMME with those of other mucosal melanomas, it appeared that PMME are characterized by a relative higher percentage of NRAS mutations. PMME seem to show a specific pattern of genetic alterations suggesting that they could represent a distinct entity among mucosal melanomas.

Lung to finger circulation time in sleep study and coronary artery calcification: the Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Lung to finger circulation time (LFCT) measured from sleep studies may represent a novel physiologic marker for cardiovascular risk in patients with sleep disordered breathing (SDB). We hypothesized that sleep study-derived LFCT would improve risk classification of markers of subclinical cardiovascular disease. METHODS: We included participants in the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep cohort with moderate-severe SDB (apnea hypopnea index [AHI] ≥ 15/hr) (N = 598). RESULTS: Those with average LFCT above the median (19.4 s) (vs. shorter LFCT) tended to be older, more obese and male. In multivariable analysis, no significant associations were found between average LFCT and subclinical cardiovascular markers including coronary artery calcium, carotid intima-media thickness or left ventricular hypertrophy. However, there was modest improvement in risk classification of coronary artery calcification as compared with AHI alone when average LFCT was added to AHI (C statistics 0.53 vs. 0.62, p = 0.0066). CONCLUSIONS: In conclusion, LFCT may be a useful addition to conventional SDB metrics to improve cardiovascular risk assessment.

Difference in spectral power density of sleep EEG between patients with simple snoring and those with obstructive sleep apnoea.

Patients with simple snoring (SS) often complain of poor sleep quality despite a normal apnoea-hypopnoea index (AHI). We aimed to identify the difference in power spectral density of electroencephalography (EEG) between patients with SS and those with obstructive sleep apnoea (OSA). We compared the absolute power spectral density values of standard EEG frequency bands between the SS (n = 42) and OSA (n = 129) groups during the non-rapid eye movement (NREM) sleep period, after controlling for age and sex. We also analysed partial correlation between AHI and the absolute values of the EEG frequency bands. The absolute power spectral density values in the beta and delta bands were higher in the OSA group than in the SS group. AHI also positively correlated with beta power in the OSA group as well as in the combined group (OSA + SS). In conclusion, higher delta and beta power during NREM sleep were found in the OSA group than in the SS group, and beta power was correlated with AHI. These findings are microstructural characteristics of sleep-related breathing disorders.

Characterization of lung-to-finger circulation time in sleep study assessment: the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVES: Lung-to-finger circulation time (LFCT) measured from sleep studies may reflect underlying cardiac dysfunction. We aimed to examine the distribution of LFCT in community-dwelling men and women in order to better understand the factors determining LFCT between and within subjects. APPROACH: We included participants of the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep with polysomnography-based evidence of sleep apnea (defined by apnea hypopnea index >15 hr-1). In a randomly selected subset of the analytical dataset, we tested an automated LFCT measurement method against the visual method. Using the automated method we then scored LFCTs from all eligible respiratory events for all included participants. A multiple regression model was constructed to determine factors independently associated with average LFCT across subjects. We also explored factors that are associated with LFCT within subjects using linear mixed-effect models. MAIN RESULTS: In a subset of the cohort (N = 39) there was a high correlation in average LFCT obtained by automated and visual methods (r = 0.96). In the analysis of 596 participants, men [19.6 (2.8)] (vs. women [17.9 (2.7) s], p < 0.0001) and older age (> 69 (vs. ≤ 69) had longer average LFCT (19.4 [2.8] vs. 18.5 [2.9] s, p < 0.0001). These associations persisted in multivariable analysis. No association was found with body habitus. Within subject analysis revealed trivial associations between apnea/hypopnea duration, apnea (vs. hypopnea), nadir O2 saturation and sleep stages (NREM vs. REM) and individual LFCT. SIGNIFICANCE: Automated LFCT measurement was highly correlated with visual-based LFCT measurement. In this group of community-dwelling adults, male sex and older age were associated with higher average LFCT.

Metastatic colorectal cancer prior to expanded RAS assessment: evidence from long-term outcome analysis of a real-life cohort within a dedicated colorectal cancer unit.

BACKGROUND: Molecular assessment and treatment of metastatic colorectal cancer (mCRC) quickly evolved during the last decades, hampering longitudinal evaluation of prognostic markers. The aim of this study was to evaluate prognostic predictors of long-term survival in a retrospective series of mCRC, treated prior to the expanded RAS assessment era. METHODS: mCRC cases treated at the Città della Salute e della Scienza University Hospital (Turin, Italy) between January 2004 and December 2012 were evaluated, including cases with ≥ 5-year follow-up only. Long-term survival was defined as an overall survival (OS) ≥ 4 years based on the observed OS interquartile range values. Univariate/multivariate Cox proportional hazards regression models were performed to assess the prognostic significance of the clinical/biological features, while binary logistic regression models were used to verify their associations with long-term survival. RESULTS: Two hundred and forty-eight mCRC cases were included and analyzed. Sixty out of two hundred and forty-eight (24%) patients were long-term survivors. Univariate binary logistic regression analysis demonstrated a significant association between long-term survival and age at diagnosis < 65 (OR = 2.28, p = 0.007), single metastatic site (OR = 1.89, p = 0.039), surgical resection of metastases (OR = 5.30, p < 0.001), local non-surgical treatment of metastases (OR = 4.74, p < 0.001), and a bevacizumab-including first-line treatment schedule (OR = 2.19, p = 0.024). Multivariate binary logistic regression analysis confirmed the prognostic significance of surgical resection of metastases (OR = 3.96, p < 0.001), local non-surgical treatment of metastases (OR = 3.32, p = 0.001), and of bevacizumab-including first-line treatment schedule (OR = 2.49, p = 0.024). CONCLUSION: Long-term survival could be achieved in a significant rate of patients with mCRC even in an era of limited molecular characterization. Local treatment of metastases proved to be a significant predictor of long-term survival.

Sleep Irregularity and Risk of Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: The cardiovascular system exhibits strong circadian rhythms to maintain normal functioning. Irregular sleep schedules, characterized by high day-to-day variability in sleep duration or timing, represent possibly milder but much more common and chronic disruption of circadian rhythms in the general population than shift work. OBJECTIVES: This study aimed to prospectively examine the association between sleep regularity and risk of cardiovascular disease (CVD). METHODS: In MESA (Multi-Ethnic Study of Atherosclerosis), 1,992 participants free of CVD completed 7-day wrist actigraphy for sleep assessment from 2010 to 2013 and were prospectively followed through 2016. The study assessed sleep regularity using the SD of actigraphy-measured sleep duration and sleep-onset timing across 7 days. Incident CVD included nonfatal and fatal cardiovascular events. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for incident CVD according to SD of sleep duration and timing, adjusted for traditional CVD risk factors (including CVD biomarkers) and other sleep-related factors (including average sleep duration). RESULTS: During a median follow-up of 4.9 years, 111 participants developed CVD events. The multivariable-adjusted HRs (95% confidence intervals) for CVD across categories of sleep duration SD were 1.00 (reference) for ≤60 min, 1.09 (0.62 to 1.92) for 61 to 90 min, 1.59 (0.91 to 2.76) for 91 to 120 min, and 2.14 (1.24 to 3.68) for >120 min (p trend = 0.002). Similarly, compared with participants with a sleep timing SD ≤30 min, the HRs (95% confidence intervals) for CVD were 1.16 (0.64 to 2.13) for 31 to 60 min, 1.52 (0.81 to 2.88) for 61 to 90 min, and 2.11 (1.13 to 3.91) for >90 min (p trend = 0.002). Exclusion of current shift workers yielded similar results. CONCLUSIONS: Irregular sleep duration and timing may be novel risk factors for CVD, independent of traditional CVD risk factors and sleep quantity and/or quality.

Composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular mortality in older community-dwelling men.

AIMS: To investigate the composition of nocturnal hypoxaemic burden and its prognostic value for cardiovascular (CV) mortality in community-dwelling older men. METHODS AND RESULTS: We analysed overnight oximetry data from polysomnograms obtained in 2840 men from the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study (ClinicalTrials.gov Identifier: NCT00070681) to determine the number of acute episodic desaturations per hour (oxygen desaturation index, ODI) and time spent below 90% oxygen saturation (T90) attributed to acute desaturations (T90desaturation) and to non-specific drifts in oxygen saturation (T90non-specific), respectively, and their relationship with CV mortality. After 8.8 ± 2.7 years follow-up, 185 men (6.5%) died from CV disease. T90 [hazard ratio (HR) 1.21, P < 0.001], but not ODI (HR 1.13, P = 0.06), was significantly associated with CV death in univariate analysis. T90 remained significant when adjusting for potential confounders (HR 1.16, P = 0.004). Men with T90 > 12 min were at an elevated risk of CV mortality (HR 1.59; P = 0.006). Approximately 20.7 (5.7-48.5) percent of the variation in T90 could be attributed to non-specific drifts in oxygen saturation. T90desaturation and T90non-specific were individually associated with CV death but combining both variables did not improve the prediction. CONCLUSION: In community-dwelling older men, T90 is an independent predictor of CV mortality. T90 is not only a consequence of frank desaturations, but also reflects non-specific drifts in oxygen saturation, both contributing towards the association with CV death. Whether T90 can be used as a risk marker in the clinical setting and whether its reduction may constitute a treatment target warrants further study.

Sleep cardiac dysautonomia and EEG oscillations in amyotrophic lateral sclerosis.

STUDY OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease due to loss of motor neurons. However, the autonomic nervous system (ANS) can also be involved. The aim of this research was to assess the sleep macro- and microstructure, the cardiac ANS during sleep, and the relationships between sleep, autonomic features, and clinical parameters in a cohort of ALS patients. METHODS: Forty-two consecutive ALS patients underwent clinical evaluation and full-night video-polysomnography. Only 31 patients met inclusion criteria (absence of comorbidities, intake of cardioactive drugs, or recording artifacts) and were selected for assessment of sleep parameters, including cyclic alternating pattern (CAP) and heart rate variability (HRV). Subjective sleep quality and daytime vigilance were also assessed using specific questionnaires. RESULTS: Although sleep was subjectively perceived as satisfactory, compared with age- and sex-matched healthy controls, ALS patients showed significant sleep alteration: decreased total sleep time and sleep efficiency, increased nocturnal awakenings, inverted stage 1 (N1)/stage 3 (N3) ratio, reduced REM sleep, and decreased CAP rate, the latter supported by lower amounts of A phases with an inverted A1/A3 ratio. Moreover, a significant reduction in HRV parameters was observed during all sleep stages, indicative of impaired autonomic oscillations. CONCLUSION: Our results indicate that sleep is significantly disrupted in ALS patients despite its subjective perception. Moreover, electroencephalogram activity and autonomic functions are less reactive, as shown by a decreased CAP rate and a reduction in HRV features, reflecting an unbalanced autonomic modulation.

Bidirectional, Daily Temporal Associations between Sleep and Physical Activity in Adolescents.

This study evaluated the daily, temporal associations between sleep and daytime physical activity and sedentary behavior among adolescents from the Fragile Families & Child Wellbeing Study. A sub-sample of the cohort at age 15 (N = 417) wore actigraphy monitors for one week during the school year from which we derived daily minutes in sedentary and moderate-to-vigorous physical activity (MVPA) and nighttime sleep measures. Multilevel models tested temporal associations of nightly sleep onset, offset, duration, and sleep maintenance efficiency, with daily MVPA and sedentary behavior. More MVPA than an individual's average was associated with earlier sleep onset (p < 0.0001), longer duration (p = 0.03), and higher sleep maintenance efficiency (p < 0.0001). On days with more sedentary behavior than an individual's average, sleep onset and offset were delayed (p < 0.0001), duration was shorter (p < 0.0001), and sleep maintenance efficiency was higher (p = 0.0005). Conversely, nights with earlier sleep onset predicted more next-day sedentary behavior (p < 0.0001), and nights with later sleep offset and longer sleep duration were associated with less MVPA (p < 0.0001) and less sedentary time (p < 0.0001, p = 0.004) the next day. These bidirectional associations between sleep and physical activity suggest that promoting MVPA may help to elicit earlier bedtimes, lengthen sleep duration, and increase sleep efficiency, critical for healthy adolescent development.

Association of Daily Rest-Activity Patterns With Adiposity and Cardiometabolic Risk Measures in Teens.

PURPOSE: Emerging data indicate that the timing and rhythms of energetic behaviors may influence metabolism and obesity risk. Our aim was to derive diurnal rest-activity patterns from actigraphy in adolescents and analyze associations with adiposity measures and cardiometabolic risk factors. METHODS: Adolescents in the Project Viva cohort wore a wrist actigraph over 7 days. We derived markers of daily rest-activity patterns from actigraphy using nonparametric models, generating measurements of relative amplitude (RA). RA reflects the normalized difference in activity measured during the most active 10-hour period and the least active 5-hour period, averaged over multiple 24-hour periods. Using multivariable-adjusted linear regression models, we estimated associations of RA and its components with markers of adiposity (body mass index, waist circumference, skinfolds, dual-energy X-ray absorptiometry fat mass) and cardiometabolic health (cardiometabolic risk score, derived as the mean of five sex-specific internal z-scores for waist circumference, systolic blood pressure, high-density lipoprotein cholesterol scaled inversely, and log-transformed triglycerides and homeostatic model assessment of insulin resistance). RESULTS: A total of 778 adolescents provided at least 5 days of valid actigraphy data. The average age was 13.2 (±.9) years, 52% were female, and the average RA was .9 (±.1). A higher RA reflecting higher activity during wakefulness and lower activity during the night was associated with more favorable indices of adiposity (e.g., -.35 kg/m2 lower body mass index per each .04 units increment of RA; 95% confidence interval: -.60 to -.09). CONCLUSIONS: In this large sample of adolescents, a higher RA emerged as a novel biomarker, associated with more favorable cardiometabolic profiles.